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Abstract Details
Case Report: Application of hepatitis B virus (HBV) deep sequencing to distinguish between acute and chronic infection
Wellcome Open Res. 2021 Jan 25;5:240.doi: 10.12688/wellcomeopenres.16157.2. eCollection 2020.
Louise O Downs12, Anna L McNaughton2, Mariateresa de Cesare3, M Azim Ansari3, Jacqueline Martin4, Charles Woodrow1, Rory Bowden3, Jane Collier4, Eleanor Barnes245, Philippa C Matthews125
Author information
1Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK.
2Nuffield Department of Medicine, University of Oxford, Medawar Building, South Parks Rd, Oxford, OX1 3SY, UK.
3Wellcome Centre for Human Genetics, Wellcome Centre for Human Genetics, Oxford, OX3 9DU, UK.
4Department of Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK.
5Oxford NIHR BRC, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK.
Abstract
Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral diversity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR). The distinction between these two scenarios may be important in predicting prognosis and underpinning treatment decisions, but can be challenging based on routine laboratory tests. Through application of deep whole-genome sequencing we typed the isolate as genotype-D1, and identified several minority variants including G1764A and G1986A substitutions in the pre-core promoter and pre-core regions, which support CHB-AR rather than AHB. In the longer term, enhanced deep sequencing data for HBV may provide improved evidence to distinguish between acute and chronic infection, to predict outcomes and to stratify treatment.